两种不同的酒精摄入方式诱导的小鼠酒精性肝损伤模型比较  

Comparison of two mouse models of alcoholic liver disease induced by oral ethanol gavage or Lierber-De Carli ethanol liquid diet

作　　者：肖娟[1,2] 张瑞芬[2] 黄菲[2] 刘磊[2] 邓媛元[2] 马永轩[2] 刘冬[3] 张名位[2] 孙远明[1] 

机构地区：[1]华南农业大学食品学院,广州510642 [2]广东省农业科学院蚕业与农产品加工研究所/农业部功能食品重点实验室/广东省农产品加工重点实验室,广州510610 [3]深圳职业技术学院,深圳518055

出　　处：《中国比较医学杂志》2016年第6期11-17,共7页Chinese Journal of Comparative Medicine

基　　金：国家自然科学基金-青年科学基金项目(NSFC 31501478);广东省自然科学基金博士启动项目(2014A030310328);深圳市科技计划基础研究项目(JCYJ20140901162541286);广东省省级科技计划项目(2016B070701012)

摘　　要：目的筛选一种简便、稳定、可靠的酒精性肝损伤模型。方法通过酒精灌胃或给予LierberDe Carli酒精液体饲料8周来建立酒精性肝损伤小鼠模型。实验期间记录小鼠精神状态、摄食量和体重变化,HE染色进行病理学分析,分析血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、γ-谷氨酰转移酶(γ-GT)、碱性磷酸酶(AKP)活性,血清和肝脏总胆固醇(TC)、甘油三酯(TG)含量等肝损伤指标。结果造模8周后,两种方式均导致小鼠肝脏脂质聚集等组织病理学变化,血清ALT、AST、AKP活性、血清和肝脏TG含量均显著提高,提示出现明显肝损伤。酒精灌胃导致小鼠精神状态差,并显著减轻体重,而酒精液体饲料对小鼠精神状态和体重影响小。酒精液体饲料模型肝脏指数和血清TC水平显著增加,而且血清ALT、AST活性、血清和肝脏TG含量及肝脏脂质聚集等组织病理学变化幅度大于酒精灌胃模型,提示前者的肝损伤程度比后者严重。结论 Lieber-De Carli酒精液体饲料模型优于酒精灌胃模型。Lieber-De Carli酒精液体饲料模型相对酒精灌胃模型更适合用于酒精性肝损伤分子机制的研究和防治药物的筛选。Objective To select a simple,stable and reliable mouse model of alcoholic liver disease. Methods The mouse models of alcoholic liver disease were induced by oral gavage ethanol or Lierber-De Carli ethanol liquid diet for 8weeks. The food intake and body weight were recorded. Pathological changes were examined using HE staining. Liverinjury was assessed by the activities of serum ALT,AST,AKP and γ-GT,and serum and hepatic TC and TG. Results After modeling,both models showed significantly increased activities of serum ALT,AST,AKP,and contents of serum and hepatic TG（ P 0. 05）,indicating the successful development of alcoholic steatohepatitis. However,oral ethanol gavage led to body weight loss and weak mental state. Ethanol liquid diet less affected the body weight and mental state. Ethanol liquid diet enhanced liver to-body weight ratio and serum TC,but oral gavage of ethanol did not. The changes of serum ALT,AST,serum and hepatic TG,and hepatic steatosis in the ethanol liquid diet models were more severe than those in the oral gavage ethanol models,suggesting that Lierber-De Carli ethanol liquid diet led to more serious liver injury than oral gavage ethanol. Conclusions Lierber-De Carli ethanol liquid diet model is better than oral gavage ethanol model,and is more suitable for studies on mechanisms and evaluation of hepato-protective drugs for alcoholic liver disease.

关 键 词：酒精性肝损伤 Lierber-De Carli酒精液体饲料 灌胃 模型 动物 

分 类 号：R33[医药卫生—人体生理学]